Despite the significant progress that has been made in its treatment, diabetes represents a severe burden on the individual as well as society. Insulin dependent diabetes mellitus (Type 1 diabetes) is an autoimmune disease, where insulitis leads to the destruction of pancreatic β-cells. At the time of clinical onset of type 1 diabetes mellitus, significant number of insulin producing β cells are destroyed and only 15% to 40% are still capable of insulin production (McCulloch et al. (1991) Diabetes 40:673-679). β-cell failure results in a life long dependence on daily insulin injections and exposure to the acute and late complication of the disease. The natural history of the disease is that the remaining functional population of β-cells inevitably dies, rendering the patients dependent on exogenous insulin for life. Arrest or even the slow down of further destruction of β-cells would lead to prolonged remission period and delay the diabetes-related complications.
Insulin, which is a β-cell specific major protein and is also moderately immunogenic when used alone, has been shown in a pilot human trial to have the effect of delaying the development of diabetes mellitus (Keller et al. (1993) Lancet 341:927-928). However, it must be injected daily over long periods of time to induce the desired effect. Also, the use of insulin implicates a concern about hypoglycemia and its sequels.
Reintroduction of autoantigen, such as insulin B chain, in incomplete Freund's adjuvant (IFA), has been used in animal models of diabetes, such as NOD mice (Muir et al. (1995) J Clin Invest 95:628-634; Orban et al. (1999) Diabetes 48 Supp.1:A216-A217; Ramiya et al. (1996) J Autoimmun 9:349-356).